CellAug 4, 2026

Blocking a specific serotonin receptor outside the brain may boost immune response against colorectal cancer

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 5, 2026

Abstract

Lysergic acid diethylamide (LSD) enhances CD8⁺ T cell-mediated antitumor immunity and suppresses colorectal cancer (CRC) growth.

Activation of the serotonin receptor 5-HT_2AR by LSD may improve immune responses against tumors.
A non-brain-penetrant 5-HT_2AR agonist, IHCH-8110, selectively targets peripheral 5-HT_2AR to avoid psychedelic effects.
IHCH-8110 inhibits CRC progression by activating 5-HT_2AR on enteric glial cells, leading to increased expression of CXCL10 and interleukin (IL)-18.
This activation promotes the recruitment and polarization of CD8⁺ T cells in the tumor microenvironment.
IHCH-8110 may convert immune-cold CRC into a more immunologically responsive state, enhancing the effectiveness of PD-1 blockade.

Simplified

Cancer remains a leading cause of morbidity and mortality worldwide. While classical psychedelics have been used clinically to treat cancer-associated psychiatric disorders, their impact on tumor progression is unclear. Here, we show that by targeting the serotonin receptor 5-HT_2AR, lysergic acid diethylamide (LSD) enhances CD8⁺ T cell-mediated antitumor immunity and suppresses colorectal cancer (CRC) growth. To harness this activity while avoiding psychedelic effects, we developed IHCH-8110, a non-brain-penetrant 5-HT_2AR agonist that selectively targets peripheral 5-HT_2AR. We show that IHCH-8110 inhibits CRC progression by activating 5-HT_2AR on enteric glial cells, thereby inducing CXCL10 and interleukin (IL)-18 expression to promote CD8⁺ T cell recruitment and effector polarization within the tumor microenvironment. By converting immune-cold CRC into a more immunologically responsive state, IHCH-8110 enhances the efficacy of PD-1 blockade. Together, our findings identify enteric 5-HT_2AR signaling as a regulator of antitumor immunity and support peripheral 5-HT_2AR agonists as a therapeutic strategy for CRC immunotherapy.

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

Psychedelic ScienceIssue #50

Psilocybin beat placebo on depression scores in an NHS trial — by a lot

↗

Blocking a specific serotonin receptor outside the brain may boost immune response against colorectal cancer

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the psychedelic science brief